Optimization of the Dosage Regimen of Growth Hormone Therapy in Children Born Small for Gestational Age (SGA OPTIMIS)

This study has been completed.
Sponsor:
Collaborator:
Merck Serono S.A.S., an affiliate of Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00249821
First received: November 4, 2005
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

Multicentric, open-label, randomized, pilot comparative study in parallel groups comparing 1 group of subjects receiving 0.057 milligram/kilogram/day (mg/kg/day) or 0.40 mg/kg/week of Saizen® during 1 year to 1 group receiving 0.035 mg/kg/day (0.24 mg/kg/week) of Saizen® during 1 year after an initial 3-year treatment of recombinant human growth hormone (r-hGH) therapy with 0.057 mg/kg/day in both groups.


Condition Intervention Phase
Small for Gestational Age (SGA)
Drug: Saizen®
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimization of the Dosage Regimen With Growth Hormone Therapy in Children Born Small for Gestational Age. An Open Label, Randomized, Pilot Study, Comparing in Children Treated for 3 Years, the Efficacy of a Saizen® Treatment at the Same Dose Versus a Lower Maintenance Dose Prolonged During 1 Additional Year.

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Height Velocity [ Time Frame: Month 12 ] [ Designated as safety issue: No ]

    Height Velocity (HV) is the change in height since the previous year´s measurement and more precisely:

    HV = {(h-hp)/(d-dp)} * 365.25 [centimeter (cm)/year] where h is current height in cm, hp is previous height in cm, closest to 1 year previous, d is the current date and dp is the date of measurement of previous height, closest to 1 year previous. Additionally, d and dp have to be within 0.6 years and 1.5 years.

    HV is the mean height velocity over the interval between d and dp but is displayed as HV at d.



Secondary Outcome Measures:
  • Change From Baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12 [ Time Frame: Baseline (randomization), Month 6 and Month 12 ] [ Designated as safety issue: No ]
    Height-Standard Deviation Score (H-SDS) was calculated as height minus mean (age-and sex-matched reference) divided by standard deviation (SD) [age and sex-matched reference]. Greater H-SDS indicates greater height.

  • Height Velocity-Standard Deviation Score (HV-SDS) [ Time Frame: Month 6 and Month 12 ] [ Designated as safety issue: No ]
    Height Velocity-Standard Deviation Score (HV-SDS) was calculated as height velocity minus reference mean height velocity divided by SD of the reference mean height velocity. Greater HV-SDS indicates greater height velocity.

  • Change From Baseline in Height at Month 6 [ Time Frame: Baseline (randomization) and Month 6 ] [ Designated as safety issue: No ]
  • Change From Baseline in Bone Age at Month 12 [ Time Frame: Baseline (randomization) and Month 12 ] [ Designated as safety issue: No ]
    Bone age was assessed by a left wrist X-Ray and evaluated by the investigator according to the Greulich and Pyle method.

  • Insulin Like Growth Factor-1 (IGF-1) Levels [ Time Frame: Baseline (randomization), Month 6 and Month 12 ] [ Designated as safety issue: No ]
  • Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels [ Time Frame: Baseline (randomization), Month 6 and Month 12 ] [ Designated as safety issue: No ]
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (randomization) until Month 12 ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs): Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs that occur during treatment with the Investigational Medicinal Product (IMP).


Enrollment: 22
Study Start Date: February 2005
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saizen® 0.057 mg/kg/day
Subjects who met all inclusion/exclusion criteria were randomly assigned to 0.057 mg/kg/day in this multi-center study. Subjects were stratified at randomization according to the Height-Standard Deviation Score (H-SDS) at this time (less than [<] -2 SDS or greater than [>] -2 SDS)
Drug: Saizen®
Saizen® [somatropin (recombinant deoxyribonucleic acid [rDNA] origin) for injection], a r-hGH, is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone.
Other Name: somatropin
Experimental: Saizen® 0.035 mg/kg/day
Subjects who met all inclusion/exclusion criteria were randomly assigned to 0.035 mg/kg/day in this multi-center study. Subjects were stratified at randomization according to the H-SDS at this time (< -2 SDS or > -2 SDS)
Drug: Saizen®
Saizen® [somatropin (rDNA origin) for injection], a r-hGH, is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone.
Other Name: somatropin

  Eligibility

Ages Eligible for Study:   6 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for inclusion / randomization into this study, the subjects must fulfill all of the following criteria (if there is no inclusion phase, the inclusion criteria will be considered as inclusion criteria for randomization):

  • Written consent form signed by the parents / legal guardian, and child if possible
  • Subject born SGA and receiving a r-hGH therapy for this pathology
  • Recombinant human growth hormone (r-hGH) started at the maximal chronological age of 7 years for girls and 8 years for boys
  • Treatment with r-hGH started for at least 30 months and less than 36 months at 0.057 mg/kg/day
  • Height gain during the first 2 years of GH treatment > 1 SD compared with the initial value

Exclusion Criteria:

To be eligible for inclusion in this study the subjects must not meet any of the following criteria:

  • Known hypersensitivity to Somatropin or any of the excipients
  • Active neoplasia (either newly diagnosed or recurrent)
  • Intracranial hypertension
  • Known diabetes mellitus
  • Proliferative or preproliferative diabetic retinopathy
  • Evidence of any progression or recurrence of an underlying intra-cranial space occupying lesion
  • Obesity defined as degree 1 on the corpulence curves
  • Precocious puberty
  • Pubertal status: Tanner breast development stage > 2 for girls, and testicular volume > 4 milliliter (mL) or testicular length > 3 centimeter (cm) and/or testosterone value >1 nanomole/liter [nmol/L] (0.29 gram/mL [g/mL]) for boys For girls > 9 years and Tanner breast development stage 1: uterine size > 35 millimeter (mm)
  • Severe chronic concomitant illness such as chronic renal failure, cystic fibrosis
  • Concomitant corticoid treatment or levothyroxine treatment other than substitutive treatment, topical or inhaled treatment
  • Participation to any clinical study within the 30 days preceding study entry
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00249821

Sponsors and Collaborators
Merck KGaA
Merck Serono S.A.S., an affiliate of Merck KGaA, Darmstadt, Germany
Investigators
Study Director: Laurence Fresneau, M.D. Merck Serono S.A.S, France
  More Information

Additional Information:
Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00249821     History of Changes
Other Study ID Numbers: IMP 25735
Study First Received: November 4, 2005
Results First Received: June 28, 2012
Last Updated: December 2, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority
France: Institutional Ethical Committee

Additional relevant MeSH terms:
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014